More Thoughts on AGEs

Ouroboros looks at advanced glycation endproducts (AGEs) and age-related damage in the extracellular matrix: "The authors exposed fibroblasts to two types of [AGE-modified proteins], which had overlapping but non-identical effects on gene expression. The common features of the response to the two proteins are most intriguing, however: increased transcription of matrix metalloproteases (MMPs), which break down the extracellular matrix (ECM), and decreased transcription of ECM components like collagen and fibronectin. Taken together, these effects would result in a net weakening of the ECM, which in turn would have profoundly negative effects on organ function, ranging from skin wrinkling to cardiomyopathy. ... increased MMPs and ECM breakdown are hallmarks of fibroblast senescence, which is usually associated with DNA damage or telomere shortening - could AGEs be stimulating premature senescence, either by damaging DNA or via some other pathway?"


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